4.5 Article

Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks

Journal

EPILEPSIA
Volume 63, Issue 10, Pages 2543-2560

Publisher

WILEY
DOI: 10.1111/epi.17380

Keywords

astroglia; calcium imaging; depressed state; elevated state; epilepsy; high-throughput behavior; hyperexcitability; photic stimulation; seizure; zebrafish

Funding

  1. European Research Council [335561]
  2. Helse Midt--Norge [90158500]
  3. Norges Forskningsrad [239973, 314189]

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This study investigated neural excitability and dynamics in multiple zebrafish seizure and epilepsy models. The researchers found divergent and convergent features in spontaneous and photically evoked neural and locomotor activity. The study suggests that understanding the interplay between elevated and depressed excitability states could lead to tailored epilepsy therapies.
Objective The switch between nonseizure and seizure states involves profound alterations in network excitability and synchrony. In this study, we aimed to identify and compare features of neural excitability and dynamics across multiple zebrafish seizure and epilepsy models. Methods Inspired by video-electroencephalographic recordings in patients, we developed a framework to study spontaneous and photically evoked neural and locomotor activity in zebrafish larvae, by combining high-throughput behavioral tracking and whole-brain in vivo two-photon calcium imaging. Results Our setup allowed us to dissect behavioral and physiological features that are divergent or convergent across multiple models. We observed that spontaneous locomotor and neural activity exhibit great diversity across models. Nonetheless, during photic stimulation, hyperexcitability and rapid response dynamics were well conserved across multiple models, highlighting the reliability of photically evoked activity for high-throughput assays. Intriguingly, in several models, we observed that the initial elevated photic response is often followed by rapid decay of neural activity and a prominent depressed state. Elevated photic response and following depressed state in seizure-prone networks are significantly reduced by the antiseizure medication valproic acid. Finally, rapid decay and depression of neural activity following photic stimulation temporally overlap with slow recruitment of astroglial calcium signals that are enhanced in seizure-prone networks. Significance We argue that fast decay of neural activity and depressed states following photic response are likely due to homeostatic mechanisms triggered by excessive neural activity. An improved understanding of the interplay between elevated and depressed excitability states might suggest tailored epilepsy therapies.

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